PSYCHONEUROENDOCRINE ASPECTS ON THE METABOLIC SYNDROME
A population-based study of middle-aged menAKADEMISK AVHANDLING
som för avläggande av medicine doktorsexamen vid Göteborgs Universitet kommer att offentligen försvaras i JK-aulan, Sahlgrenska Sjukhuset, tisdagen den 24 november 1998 kl 09.00 av ROLAND ROSMONDAvhandlingen baseras på följande delarbeten:
I. Rosmond R, Lapidus L, Mårin P, Björntorp P. (1996). Mental distress,
obesity and body fat distribution in middle-aged men. Obes. Res. 4:245-252.
II. Rosmond R, Björntorp P. (1998). Endocrine and metabolic aberrations in
men with abdominal obesity in relation to anxio-depressive infirmity.
Metabolism. 47:1187-1193.
III. Rosmond R, Dallman MF, Björntorp P. (1998). Stress-related cortisol
secretion in men: relationships with abdominal obesity and endocrine,
metabolic and hemodynamic abnormalities. J. Clin. Endocrinol. Metab.
83:1853-1859.
IV. Rosmond R, Holm G, Björntorp P. (1998). Food-induced cortisol secretion
in men: relationships with abdominal obesity, hormones, metabolism and
circulation. Submitted for publication.
V. Rosmond R, Björntorp P. (1998). The hypothalamic-pituitary-adrenal axis
activity as a predictor of cardiovascular disease, Type 2 diabetes and
stroke. Submitted for publication.
PSYCHONEUROENDOCRINE ASPECTS ON THE METABOLIC SYNDROME
A population-based study of middle-aged men
Roland Rosmond, Department of Heart and Lung Diseases, Sahlgrenska
University Hospital, Göteborg University, S-413 45 Göteborg, Sweden.
Background: Abdominal obesity is associated with prevalent and serious
diseases. The causes of abdominal obesity are most likely to be both
genetic and environmental. Among the latter factors a hypersensitive
hypothalamic-pituitary-adrenal (HPA) axis followed by an inadequate
cortisol secretion has been suggested.
Aims: To investigate the effect of psychological distress on abdominal
obesity and the regulation of cortisol secretion. Furthermore, to examine
the peripheral consequences of an inadequate cortisol secretion, by means
of newly developed techniques for the assessment of cortisol, and to
evaluate the impact of the HPA axis activity on established risk factors
for cardiovascular disease (CVD), Type 2 diabetes mellitus and stroke.
Subjects and Methods: A population of 1302 men born 1944 was selected from
the city of Göteborg, Sweden. They were providing responses to a
questionnaire and self-measurements of height, weight, and circumferences
over the waist and hips. Subgroups of the waist/hip circumference ratio
(WHR) (n=284) were then invited for an examination including measurements
of anthropometry (body mass index, BMI, kg/m2, WHR and abdominal sagittal
diameter, D), hormones (testosterone and insulin-like growth factor I,
IGF-I), metabolism (overnight fasting values of insulin, glucose,
triglycerides, total-, LDL- and HDL-cholesterol), and circulation (systolic
and diastolic blood pressures and heart rate). Furthermore, salivary
cortisol concentrations were determined on repeated (n=7) occasions over a
random working day, and perceived stress reported in parallel. A
standardised lunch was used as a physiological challenge. A low dose (0.5
mg) dexamethasone suppression test was also performed.
Results: The WHR showed significant and independent relationships to the
use of psycho-pharmacological drugs, depressive symptoms and sleep
disturbances. A blunted dexamethasone suppression of cortisol was found in
a subgroup of men with anxiety and depression and elevated BMI, WHR, and D.
In addition, with an inadequate cortisol secretory pattern, stress-related
cortisol secretion showed strong relationships to elevated BMI, WHR and D,
all metabolic measurements except HDL, which was low. Blood pressure and
heart rate were elevated, and testosterone and IGF-I were low. After
stimulation of cortisol secretion by food intake, positive associations
were found with BMI, waist and hip circumferences, WHR and D, as well as
insulin, glucose and the insulin/glucose ratio, total and LDL cholesterol,
blood pressures and heart rate. Furthermore, under the influence of such an
abnormal cortisol secretory pattern, the risk factors for CVD, Type 2
diabetes and stroke congregated into one distinct, strongly intercorrelated
cluster. In contrast, a normal cortisol secretory pattern was associated
with low values of total and LDL cholesterol as well as blood pressures,
and high IGF-I.
Conclusions: The results suggest that the function of the HPA axis is of
fundamental importance for anthropometric, endocrine, metabolic and
hemodynamic factors. When perturbed, the development of abdominal obesity,
endocrine abnormalities, insulin resistance and hypertension follow,
leading to serious diseases. This syndrome is based on environmental
pressures in genetically vulnerable subjects.
Key words: HPA axis, cortisol, abdominal obesity, hormones, metabolism,
circulation, anxiety, depression, stress.
ISBN 91-628-3195-X
ROLAND ROSMOND, Hjärtlunginstit, SU Sahlgrenska, 413 45 Göteborg
